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Review of spaceflight and hindlimb suspension unloading induced sarcomere damage and repair.

Hindlimb suspension unloading (HSU) and spaceflight microgravity induce atrophy of the slow adductor longus muscle fibers which, following reloading, exhibit eccentric contraction (EC)-like lesions (abnormal widening of sarcomeres with A band disruption and excessively wavy, extracted Z lines). These lesions are similar morphologically to those produced in normal muscles after strenuous eccentric exercise. It appears that atrophic muscles exhibit increased susceptibility to eccentric damage because lesions are produced during nonstressful voluntary movements upon return to weightbearing. The EC-like lesions are absent in the unweighted conditions, but appear in HSU rats 15-60 minutes after reloading and in space-flown rates about 4 hrs after landing. By 12 hours, many EC-like lesioned sarcomeres are fully covered by longitudinal patches of Z line-like material which increases in density by 48 hours, producing the so-called "Z line streaming" morphology. In this case, Z line streaming is indicative of rapid repair of damaged sarcomeres rather than the onset of sarcomere breakdown. Immunoelectron microscopy is necessary to determine the composition of this dense material. By 9 days of reloading at 1 gravity, sarcomeres have regained normal structure, except for very rare persistence of faint Z patches. The morphological data indicate that Z patches serve at least two functions: 1) to permit contractile force to be transmitted across the damaged sarcomeres and 2) to provide a scaffold upon which sarcomeres are reconstructed in an active functional muscle.

Animals↗

Recruitment of the Rhesus soleus and medial gastrocnemius before, during and after spaceflight.

Electromyograms were recorded from the soleus and medial gastrocnemius muscles and tendon force from the medial gastrocnemius muscle of 2 juvenile Rhesus monkeys before, during and after Cosmos flight 2229 and of ground control animals. Recording sessions were made while the Rhesus were performing a foot pedal motor task. Preflight testing indicated normal patterns of recruitment between the soleus and medial gastrocnemius, i.e. a higher level of recruitment of the soleus compared to the medial gastrocnemius during the task. Recording began two days into the spaceflight and showed that the media gastrocnemius was recruited preferentially over the soleus. This observation persisted throughout the flight and for the 2 week period of postflight testing. These data indicate a significant change in the relative recruitment of slow and fast extensor muscles under microgravity conditions. The appearance of clonic-like activity in one muscle of each Rhesus during flight further suggests a reorganization in the neuromotor system in a microgravity environment.

Animals↗

Effects of 17 days of head-down bed rest on hydro-electrolytic regulation in men.

Prolonged periods of head-down bed rest (HDBR) are commonly used to mimic the effects of microgravity. HDBR has been shown to produce, as in space, a cephalad redistribution of circulating blood volume with an increase in central blood volume which induces the early adaptations in blood volume regulating hormones. Changes in atrial natriuretic peptide (ANP), arginine vasopressin (AVP), renin activity and aldosterone have been observed. Many reports describe these endocrine adaptations but few investigations of rhythms are in the literature. We proposed to evaluate the circadian rhythms of the hormones and electrolytes involved in the hydro-electrolytic regulation during a HDBR study which was designed to simulate a 17-day spaceflight (Life and Microgravity Spacelab experiment, LMS, NASA).

Adult↗

Cyclic AMP-receptor proteins in heart muscle of rats flown on Cosmos 1887.

A frequent cellular response to organismal stress is the increase in ligand binding by beta-adrenergic receptors. The extracellular signal is amplified by intracellular increases in cyclic AMP and the ensuing activation of cyclic AMP-dependent protein kinase (cAPK). The molecular mechanisms involve the binding of cyclic AMP to regulatory (R) subunits of cAPK, thus freeing the catalytic subunit for protein phosphorylation. This study was carried out to determine the cellular compartmentalization of the cyclic AMP-receptor proteins in heart ventricular tissue obtained from rats flown on the Cosmos 1887 mission. Photoaffinity labeling of soluble and particulate cell fractions with an [32P]-8-azido analog of cyclic AMP was followed by electrophoretic separation of the proteins and by autoradiographic identification of the labeled isoforms of cAPK R subunits. The results showed that RII in the particulate subcellular fraction was significantly decreased in heart cells from rats in the flight group when compared to controls. Protein banding patterns in both the cytoplasmic fraction and in a fraction enriched in chromatin-bound proteins showed some variability in tissues of individual animals, but exhibited no changes that could be directly attributed to flight conditions. No significant change was apparent in the distribution of RI or RII cyclic AMP binding in the soluble fractions. These findings indicate that the cardiac cell integrity or its protein content is not compromised under flight conditions. There is, however, what appears to be an adaptive molecular response which can be detected using microanalytical methods, indicating that a major hormone regulated mechanism may be affected during some phase of travel in space.

Animals↗

Neuromuscular aspects in development of exercise countermeasures.

Based on the results generated from experiments conducted by our investigators, it is clear that prolonged exposure to microgravity environments can induce ultrastructural abnormalities and atrophy of muscle and impair muscle function, especially upon return to terrestrial gravity. It is also apparent that ground-base models can be effectively used to study these changes. This provides a less expensive and more controlled laboratory condition in order to conduct experiments. The use of animal models must be more closely examined. In the case of muscle adaptations to microgravity, the data from flight experiments which have used rodents might suggest the use of exercise with characteristics contrary to those which would be most appropriate to defend against atrophy and dysfunction in human muscle. Although many spaceflight experiments may be limited to the use of animal models, the results of the studies reviewed in this paper emphasize the importance of using human models in order to provide the most accurate interpretation of data for the development of exercise countermeasures for spaceflight. If maintenance of muscle structure, size and function is perceived as operationally necessary, the results from the studies conducted by our investigators indicate that the use of more resistive exercise must be given greater consideration as part of the development of future exercise countermeasure programs for spaceflight. The advantages of incorporating resistive exercise with a strong emphasis on the use of eccentric muscle actions in addition to concentric actions may prove most effective as a countermeasure against the muscle atrophy and dysfunction caused by long-duration exposure to microgravity environments.

Adult↗

Interactive effects of nutrition, environment, and rat-strain on cortical and vertebral bone geometry and biomechanics.

Because of differences between rodent experiments on USSR and USA spaceflights, the present experiment was designed to generate comparative data about the sensitivity of cortical (humerus) and vertebral (T7) bones to cage environment, diet, and rat-strain differences. For 2 weeks (48-62 d), male Taconic-Sprague-Dawley and Czechoslovakian-Wistar rats were maintained in flight-simulation cages (1 rat/cage = USA, 10 rats/cage = USSR) and fed either USSR or USA diets. All rats increased (greater than 60%) their body mass during the two weeks, and there were no differences among humeral lengths for the different groups. Rats in USSR cages had significantly larger total and medullary cross-sectional areas for the humerus, and the cross-sectional areas of T7 of Taconic rats were greater than the Czech rats. USSR caging resulted in significantly enhanced structural and material properties in rat humeri, while the USA diet produced significantly greater humeral maximum and failure loads. The flexural rigidity of the Czech-rat humeri was significantly greater than the Taconic rats. Humeri from Czech rats on the USA diet had significantly greater material properties in the elastic-loading region than did Taconic rats on the USSR diet. Further, the humeral failure loads of Taconic rats on the USSR diet were more adversely affected by USA cages than were the Czech rats on the USSR diet. In T7 vertebrae, no significant structural differences were found among the groups, but material properties were influenced by all three factors; generally, the combination of factors that produced the significantly greater T7 material properties was: USSR caging, USSR diet, and the Czech strain of rat.

Animal Nutritional Physiological Phenomena↗

A study of the effects of prolonged simulated microgravity on the musculature of the lower extremities in man: an introduction.

The reduction of muscle strength and size of the lower extremities has been observed following spaceflight. However, there are virtually no data from direct measurements of muscle tissue which provide a means of understanding the physiological alterations associated with the impaired function. We therefore conducted a study in which eight healthy men underwent 30 days of continuous exposure to 6 degrees headdown tilt as an analogue for space microgravity. We used percutaneous muscle biopsy, computed tomography, anthropometry, and in vivo muscle strength measures under controlled experimental conditions to provide new data about mechanical, structural, and metabolic characteristics of skeletal muscle in man following exposure to microgravity.

Adult↗

Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity.

The purpose of these experiments was to test the hypothesis that reduced size of the leg muscle compartment following exposure to long-duration microgravity would be associated with increased leg compliance. Eight men, 31-45 years of age, were measured for vascular compliance of the calf and serial circumferences of the thigh and calf before, during and after 30 d of continuous 6 degrees head-down bedrest. Cross-sectional areas (CSA) of muscle, fat, and bone compartments in the thigh and calf were determined pre- and post-bedrest by computed tomography. Calculated leg volumes decreased (p less than 0.05) in the calf by 9.9% and in the thigh by 4.5% from pre- to post-bedrest. Muscle compartment CSA also decreased (p less than 0.05) in both calf (-4.8%) and thigh (-8.1%); leg compliance (vol%/mm Hg x 100) increased (p less than 0.05) from 3.9 +/- 0.7 to 4.9 +/- 0.5. Calf compliance measured before and after bedrest was inversely related to calf muscle compartment CSA (r = -0.61, p less than 0.05) and the percent decrease in calf muscle compartment CSA from pre- to post-bedrest was inversely correlated with an increase in calf compliance (r = -0.72, p less than 0.05). Increased leg compliance following long-duration spaceflight is associated with reduced size of the leg muscle compartment.

Adipose Tissue↗

Factors in daily physical activity related to calcaneal mineral density in men.

To determine the factors in daily physical activity that influence the mineral density of the calcaneus, we recorded walking steps and the type and duration of exercise in 43 healthy 26-to 51-yr-old men. Areal (g.cm-2) calcaneal bone mineral density (CBMD) was measured by single energy x-ray densitometry (SXA, Osteon, Inc., Wahiawa, HI). Subjects walked a mean (+/- SD) of 7902 (+/- 2534) steps per day or approximately 3.9 (+/- 1.2) miles daily. Eight subjects reported no exercise activities. The remaining 35 subjects spent 143 (2-772) (median and range) min.wk-1 exercising. Twenty-eight men engaged in exercise activities that generate single leg peak vertical ground reaction forces (GRFz) of 2 or more body weights (high loaders, HL), and 15 reported exercise or daily activities that typically generate GRFz less than 1.5 body weights (low loaders, LL). CBMD was 12% higher in HL than LL (0.668 +/- 0.074 g.cm-2 vs 0.597 +/- 0.062 g.cm-2, P < 0.004). In the HL group, CBMD correlated to reported minutes of high load exercise (r = 0.41, P < 0.03). CBMD was not related to the number of daily walking steps (N = 43, r = 0.03, NS). The results of this study support the concept that the dominant factor in daily physical activity relating to bone mineral density is the participation in site specific high loading activities, i.e., for the calcaneus, high calcaneal loads.

Absorptiometry, Photon↗

[Determination of six main components in compound theophylline tablet by convolution curve method after prior separation by column partition chromatography].

On a partition chromatographic column in which the support is Kieselguhr and the stationary phase is sulfuric acid solution (2 mol/L), three components of compound theophylline tablet were simultaneously eluted by chloroform and three other components were simultaneously eluted by ammonia-saturated chloroform. The two mixtures were determined by computer-aided convolution curve method separately. The corresponding average recovery and relative standard deviation of the six components were as follows: 101.6, 1.46% for caffeine; 99.7, 0.10% for phenacetin; 100.9, 1.31% for phenobarbitone; 100.2, 0.81% for theophylline; 99.9, 0.81% for theobromine and 100.8, 0.48% for aminopyrine.

Aminopyrine↗

Response of the neuromuscular unit to spaceflight: what has been learned from the rat model.

Despite the inherent limitations placed on spaceflight investigations, much has been learned about the adaptations of the neuromuscular system to weightlessness from studies of rats flown for relatively short periods (approximately 4-22 days). Below is a summary of the major effects of spaceflight observed in muscles of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy rapidly during spaceflight; significant atrophy is observed as early as after 4 days of flight. 2. The atrophic response appears to be related to the primary function of the muscle. In the hindlimb, the relative amount of atrophy can be characterized as slow extensors > fast extensors > fast flexors. This pattern of relative atrophy does not appear to be occurring in the forelimb; however, not enough data are available to draw any definitive conclusions at this time. 3. Both slow and fast fibers atrophy during spaceflight, with the largest fibers within an individual muscle generally showing the greatest atrophic response. Interestingly, the amount of fiber atrophy appears to reach a plateau after about 14 days of flight. 4. Adaptations have been observed in the concentration and content of all muscle proteins pools, with the protein pools in slow muscles the most affected. 5. Some slow and fast fibers in predominantly slow and fast muscles show shifts in their histochemical and biochemical properties, toward those observed in a "faster" phenotype. 6. Some fibers, presumably expressing slow MHC isoforms before flight, begin to express fast MHC isoforms during flight. 7. The oxidative capacity of the muscles or fibers is relatively unaffected by spaceflight, particularly in the slow muscles. Any change in whole-body fatigability associated with spaceflight most likely reflects the loss in muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle fibers is enhanced after spaceflight. This metabolic adaptation seems to be related to the shift in the contractile proteins towards "faster" isoforms. 9. The vascularity of muscles appears to be maintained after flight, based, at least, on histological observations of capillarity. 10. The force capabilities of the muscles and fibers appear to decrease in parallel with the decreases in size, i.e., the specific tension is not significantly affected after flight. 11. Changes in the speed-related properties of the slow muscles are consistent with the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in the slow muscles become "faster." 12. Some muscle fiber and neuromuscular junction damage has been observed after flight, particularly in the slow muscles. The extent of damage may be related to the amount of time that the muscles are allowed to reload before removal, i.e., in general, shorter intervals result in less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory (spinal ganglia) neurons have been quite variable, but this may be related to the amount of time that the muscles are allowed to reload before removal. Morphological adaptations after relatively short periods of reloading may reflect a decrease in the activation of the neural elements during flight.

Adaptation, Physiological↗